Circular RNAs (circRNAs) have caught increasing attentions and interests for their important involvement in cancer initiation and progression. This study aims to investigate the biological functions of circNOL10 and its potential molecular mechanisms in breast cancer (BC). qRT-PCR and western blot assays were performed to measure the expression of related genes. CCK-8, colony formation, flow cytomerty and transwell assays were used to assess cell proliferation, cell cycle, migration and invasion. RNA pull-down, luciferase reporter and RIP assays were applied to address the potential regulatory mechanism of circNOL10. CircNOL10 was down-regulated in BC tissues and cells. Low expression of circNOL10 was associated with larger tumor size, advanced TNM stage, lymph node metastasis and unfavorable prognosis. Overexpression of circNOL10 inhibited cell proliferation, migration, invasion and EMT in vitro and slowed xenograft tumor growth in vivo. Mechanistically, circNOL10 could act as a molecular sponge for miR-767-5p, leading to the up-regulation of suppressors of cytokine signaling 2 (SOCS2) and inactivation of JAK2/STAT5 pathway. Moreover, circNOL10-mediated suppression of malignant phenotypes was attenuated by miR-767-5p. Similar to circNOL10, enforced expression of SOCS2 also resulted in the suppression of cell proliferation and metastasis. Furthermore, knockdown of SOCS2 reversed the tumor-suppressive effect induced by circNOL10. CircNOL10 repressed BC development via inactivation of JAK2/STAT5 signaling by regulating miR-767-5p/SOCS2 axis. Our findings offer the possibility of exploiting circNOL10 as a therapeutic and prognostic target for BC patients.

中文翻译：

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CircNOL10 通过海绵 miR-767-5p 调节 SOCS2/JAK/STAT 信号传导抑制乳腺癌进展

环状RNA（circRNA）因其在癌症发生和进展中的重要参与而引起越来越多的关注和兴趣。本研究旨在探讨circNOL10的生物学功能及其在乳腺癌（BC）中的潜在分子机制。进行 qRT-PCR 和蛋白质印迹分析以测量相关基因的表达。CCK-8、集落形成、流式细胞仪和 transwell 测定用于评估细胞增殖、细胞周期、迁移和侵袭。应用 RNA 下拉、荧光素酶报告基因和 RIP 分析来解决 circNOL10 的潜在调控机制。CircNOL10 在 BC 组织和细胞中下调。circNOL10的低表达与较大的肿瘤大小、晚期TNM分期、淋巴结转移和不良预后相关。circNOL10 的过表达在体外抑制细胞增殖、迁移、侵袭和 EMT，并在体内减缓异种移植肿瘤的生长。从机制上讲，circNOL10 可以作为 miR-767-5p 的分子海绵，导致细胞因子信号 2 (SOCS2) 抑制因子的上调和 JAK2/STAT5 通路的失活。此外，miR-767-5p减弱了circNOL10介导的恶性表型抑制。与 circNOL10 类似，SOCS2 的强制表达也导致细胞增殖和转移的抑制。此外，SOCS2 的敲低逆转了 circNOL10 诱导的肿瘤抑制作用。CircNOL10 通过调节 miR-767-5p/SOCS2 轴使 JAK2/STAT5 信号失活来抑制 BC 的发展。